2-chloro-5-n-pentylresorcinol

ABSTRACT

1. THE COMPOUND 2-CHLORO-5-N-PENTYLRESORCINOL.

United States Patent 3,850,997 Z-CHLORO-5-n-PENTYLRESORCINOL ArnoldBrossi, Verona, and Antonino Focella and Sidney Teitel, Clifton N.J.,assignors to Hoffmann-La Roche Inc., Nntley, NJ.

No Drawing. Original application Jan. 22, 1969, Ser. No. 793,191, nowabandoned. Divided and this application Sept. 16, 1971, Ser. No. 181,227

Int. Cl. C07c 39/24 US. Cl. 260-623 R 1 Claim ABSTRACT OF THE DISCLOSUREPreparation of S-alkyl substituted resorcinols such as olivetol fromaliphatic aldehydes and intermediates in this process.

This is a division of application Ser. No. 793,191, filed J an. 22,1969, now abandoned.

BACKGROUND OF THE INVENTION In the past, olivetol [S-n-amyl-resorcinol]and other S-alkyl substituted resorcinols have been synthesized fromstarting materials such as 3,5-dihydroxybenzoic acid. These procedureshave proven extremely disadvantageous due to the fact that the startingmaterials are not readily available. Consequently, these processes haveproven extremely costly. Therefore, it has long been desired to providea simple and economic process for producing S-alkyl substitutedresorcinols from inexpensive starting materials.

SUMMARY OF THE INVENTION In accordance with this invention, it has beenfound that S-alkyl resorcinols of the formula:

wherein R is an alkyl group containing from 1 to 26 carbon atoms,

can be synthesized economically and in high yields through thecondensation product of acetone and an aldehyde of the formula:

R--CHO II wherein R is as above. In this manner, resorcinols of theformula I above, such as olivetol, can be economically prepared fromcheap and readily available starting materials.

DETAILED DESCRIPTION The term lower alkyl as used herein denotes bothstraight and branched chain alkyl groups containing from 1 to 7 carbonatoms such as methyl, ethyl, propyl, isopropyl, etc. The term loweralkanoic acid denotes lower alkanoic acids having from 1 to 7 carbonatoms such as formic acid, acetic acid, propionic acid, etc. The termlower alkanol denotes alkanols containing from 1 to 7 carbon atoms suchas methanol, ethanol, propanol, isopropanol, etc. The term phenyl-loweralkyl as used throughout the specification denotes phenyl-lower alkylgroups containing from 7 to 14 carbon atoms such as benzyl, phenethyl,phenpropyl, etc.

The term alkyl group containing from 1 to 26 carbon atoms in formula Iabove includes both straight and branched chain alkyl groups containingfrom 1 to 26 carbon atoms such as methyl, ethyl, n-propyl, isopropyl,n-decyl, dodecyl, n-pentadecyl, octadecyl, heneicosyl,1,2,3-trimethylheptyl, 1,2-dimethyloctyl, etc. In accord- 3,850,997Patented Nov. 26, 1974 ice wherein R is as above. This condensationreaction is carried out by reacting a compound of the formula II withacetone in the presence of an alkali metal hydroxide such as sodiumhydroxide, potassium hydroxide, etc. In carrying out this reaction,excess acetone can be utilized as the reaction medium. However, ifdesired, an inert organic solvent can be utilized as the reactionmedium. If desired, any conventional inert organic solvent can be usedas the reaction medium. Among the conventional inert organic solventswhich can be utilized, toluene, benzene, xylene, dioxane, ethyl etherand tetrahydrofuran are preferred. This reaction can be carried out atroom temperature. However, if desired, elevated or reduced temperatures,i.e., temperatures between 10 C. to 70 C. can be utilized.

The next step of the process of this invention is carried out bydehydrating the compound of formula III above to form a compound of theformula:

0 R-oH=oH( ioHa wherein R is as above.

Any conventional method of dehydrating the compound of the formula IIIabove can be utilized in carrying out this reaction. Among theconventional dehydrating methods which can be utilized are includedtreating the compound of the formula III above with a dehydrating agentsuch as sodium sulfate, cupric sulfate, etc. This dehydration reactioncan be carried out in an anhydrous solvent medium utilizing refluxtemperatures. Another means for dehydrating the compound of the formulaIII above is by refluxing the compound of the formula III in anazeotroping agent such as a conventional azeotropic solvent. Among theazeotropic solvents which are utilized to dehydrate the compound of theformula III above, benzene, xylene, toluene, etc., are preferred.

In the next step, the compound. of formula IV is converted to a compoundof formula:

wherein R is as above, and R is lower alkyl or phenyllower alkyl byreacting the compound of formula IV with a malonic acid ester of theformula:

wherein R is a lower alkyl or phenyl-lower alkyl. This reaction iscarried out in an organic solvent in the presence of a base. Anyconventional base can be utilized in carrying out this reaction. Amongthe conventional bases which can be utilized in accordance with thisinvention are included alkali metal hydroxides, such as sodium orpotassium hydroxide, alkali metal amides such as sodamide, etc., alkalimetal alcoholates; alkali metal hydrides such as sodium hydride,potassium hydride, etc.; basic amines such as pyridine, etc. Thepreferred bases are alkali metal alkoxides such as sodium methoxide andpotassium methoxide.

In this reaction between compounds of the formula VI above withcompounds of the formula IV above, any conventional organic solvent canbe utilized. Among the conventional solvents, the lower alkanols such asmethanol, ethanol, etc., are preferred. Where a lower alkanol containingless carbon atoms than R in the compound VI above is utilized as theorganic solvent, this alkanol forms the ester group in compounds of theformula V.

' The reaction of compounds of the formula IV above with compounds ofthe formula VI above to produce the compound of the formula V above canbe carried out by reacting one mole of the compound of the formula IVabove with one mole of the compound of the formula VI above. In thisreaction, a molar excess of either the compound of formula VI above orthe compound of the formula IV above can be present. Furthermore, it isgenerally preferable that the base be present in the reaction medium inan amount of at least one mole per mole of the compound of formula IVabove. However, if desired, the base can be present in excess of thisamount. In carrying out this reaction, temperature and pressure are notcritical, and this reaction can be carried out at room temperature andatmospheric pressure. If desired, elevated or reduced temperatures canbe utilized. Generally, this reaction can be conveniently carried out ata temperature of from C. to 100 C. depending upon the reflux temperatureof the solvent.

In accordance with this invention, the compound of the formula V abovecan be converted into the compound of the formula I above by thefollowing reaction scheme:

wherein R and R are as above, and X is selected from the groupconsisting of chlorine, bromine or iodine.

In accordance with one embodiment of this invention, the compound of theformula V above is converted to the compound of the formula I above, viathe compound of the formula VII above. In the first step of thisreaction sequence, step (a), the compound of the formula V above isconverted to the compound of the formula VII above. The reaction of step(a) is carried out by treating the compound of the formula V above witha halogenating agent wherein the halogen is bromine, chlorine or iodine.Any conventional halogenating agent can be utilized in carrying out thereaction of step (a). Among the conventional halogenating agents Whichcan be utilized are included, N-bromo-succinimide, alkali metalhypohalites, cupric bromide, cupric iodide or cupric chloride, or ahalogen such as bromine, chlorine or iodine. Generally, this reaction iscarried out in an inert solvent. Any conventional inert solvent can beutilized in carrying out this reaction. Among the conventional inertsolvents which can be utilized in carrying out this reaction, Water,acetone, ethanol and the organic acids such as acetic acid, propionicacid, etc., are preferred. Among the organic acid solvents, the loweralkanoic acids such as acetic acid are preferred. It is generallypreferable to utilize water or aqueous organic acids which include loweralkanoic acids such as aqueous acetic acid in carrying out thisreaction. When a halogen such as bromine, chlorine, or iodine isutilized, this halogen is generally added to the reaction mixturedissolved in the inert organic solvent.

In carrying out the reaction of step (a), it is preferable to add about1 mole of the halogenating agent per mole of the compound of formula Vabove. If desired, a molar excess of the halogenating agent can beutilized in the reaction, i.e., from about 1 to 3.5 moles of thehalogenating agent per mole of the compound of formula V above. Ifdesired, this reaction can be carried out at room temperature. However,any temperature from about 0 C. to about 30 C. can be utilized incarrying out this reaction.

The conversion of compounds of the formula VII above to compounds of theformula I above, is carried out by heating the compound of the formulaVII above to a temperature of from 40 C. to 130 C. It is generallypreferred to carry out the reaction in the presence of inorganic acid oracid salt of organic bases. The presence of these acid or acid saltsspeeds up the reaction. Typical inorganic acids which may be employed inthe above process include hydrohalic acids (especially hydrochloric orhydrobromic acid) and sulfuric acid, as Well as the mineral acid saltsof organic bases such as pyridine, with pyridine hydrochloride beingpreferred. This reaction can be carried out in an aqueous or organicsolvent medium. Any conventional inert organic solvent can be utilizedas the reaction medium. On the other hand, the reaction of step (b) cantake place without the use of any solvent such as by heating thecompound of formula VII above to a temperature of from 40 to F. Thisreaction of step (b) can take place at atmospheric pressure. However, ifdesired, elevated pressures can be utilized, i.e., from 50 p.s.i.g. to1,000 p.s.i.g.

In accordance with another embodiment of this invention, the compound ofthe formula V above can be directly converted to the compound of theformula I above by treating the compound of the formula V above with ahalogenating agent in an inert solvent medium, at a temperature of from40 C. to C. Any of the conventional halogenating agents such as thosementioned hereinbefore can be utilized in carrying out the reaction ofstep (c). The halogen should be either chlorine, bromine or iodine.Among the preferred halogenating agents are included cupric halides,such as cupric bromide, cupric chloride, cupric iodide, bromine,chlorine and iodine. In carrying out the reaction of step (c), anyconventional inert solvent can be utilized. Generally, the preferredsolvents are water and the organic acids which include lower alkanoicacids such as acetic acid, propionic acid, etc., or high boiling inertorganic solvents such as xylene, etc. The reaction of step (c) ispreferably carried out at the reflux temperature of the reaction medium.However, temperatures of from about 40 C. to about 130 C. can beutilized, depending upon the reflux temperature of the solvent medium.While reaction temperatures of from 40 C. to 130 C. can be utilized tocomplete the reaction, the addition of the halogenating agent to thecompound of formula V above should take place at lower temperatures,i.e., from about 0 to 20 C,

In accordance with another embodiment of this invention, the compoundsof formula V above can be converted to the compound of formula I abovevia the compound of the formula VIII above. In this reaction sequence,the compound of the formula V above is first converted to the compoundof the formula VIII above via reaction step (d). The reaction of step(d) is carried out by treating the compound of the formula V above witha dehydrogenating agent. In carrying out this reaction, any conventionaldehydrogenating agent can be utilized. Among the conventionaldehydrogenating agents which can be utilized, dichlorodicyanoquinone,mercuric acetate and palladium on carbon are preferred. Generally, thisreaction is carried out in a conventional inert organic solvent. Anyconventional inert organic solvent can be utilized. Among theconventional inert organic solvents that can be utilized in thisreaction, benzene, toluene, xylene, organic acids which include loweralkanoic acids such as acetic acid are preferred. When palladium oncarbon is utilized as the dehydrogenating agent, no solvent need bepresent and the reaction can be carried out by heating the compound to atemperature of from about 150 C. to about 300 C. When a solvent isutilized, the reaction proceeds very slowly at room temperature.Therefore, it is generally preferred to utilize elevated temperatures incarrying out this reaction. In general, temperatures from about 50 C. to120 C. are preferred depending upon the reflux temperature of thesolvent utilized in the reaction medium.

The compound of formula VIII above can, if desired, be prepared from thecompound of formula VII above via reaction step (e). This reaction iscarried out by treating the compound of the formula VII above withorganic amine base. Any conventional organic amine base such as thebases hereinbefore mentioned can be utilized. Among the conventionalbases which can be utilized, pyridine, triethanolamine, etc., arepreferred. In carrying out the reaction of step (e), an inert organicsolvent medium can be utilized. Any conventional inert organic solventcan be utilized in carrying out this reaction. Among the conventionalinert organic solvents, solvents such as benzene, Tetralin, Decalin,xylene and 1,2,4-trichlorobenzene are preferred. This reaction ispreferably carried out at temperatures of from about 40 C. to 150 C.,depending upon the reflux temperature of the reaction medium. However,this reaction can be easily carried out at room temperature, i.e.,temperatures of from 20 C. to 35 C.

The compound of formula VIII above is converted to the compound offormula I above via reaction step (f). The reaction step (f) is carriedout by first saponifying the compound of the formula VIII above with anyconventional saponifying agent to form the compound of the formula VIIIabove wherein R is hydrogen and thereafter decarboxylating the compoundof the formula VIII above. In saponifying the compound of the formulaVIII, any conventional saponifying agent and method of saponificationcan be utilized. Among the conventional saponifying agents which can beutilized are included the inert alkali metal hydroxides such as sodiumhydroxide and potassium hydroxide utilizing conventional inert organicsolvents or an aqueous medium. In carrying out the saponificationreaction, temperature and pressure are not critical, and this reactioncan be carried out at room temperature and atmospheric pressure.However, elevated temperatures up to the reflux temperature of thesolvent can be utilized.

The decarboxylation step is carried out by treating the saponifiedcompound of formula VIII above with an inorganic acid. Any of theconventional inorganic acids such as the hydrohalic acids can beutilized in carrying out this reaction. This reaction can be carried outin an inert organic solvent or aqueous medium. In carrying out thisreaction, temperature and pressure are not critical. Therefore, thisreaction can be carried out at room temperature and atmosphericpressure. However, if desired, elevated or reduced temperatures andpressures can be utilized.

In accordance with another embodiment of this invention, the compound ofthe formula V above can be con- 1 verted to the compound of the formulaI above via the compound of the formula IX above. In the first step ofthis reaction, the compound of formula V above is converted to thecompound of formula IX above via reaction step (g). The reaction step(g), is carried out by treating the compound of the formula V with ahalo genating agent in the presence of an organic base preferablypyridine. In carrying out the reaction of step (g), the halogen of thehalogenating agent utilized should be bromine, chlorine or iodine, andat least 2 moles of the halogenating agent should be present per mole ofthe compound of the formula V above. Any of the halogenating agentsdescribed in connection with step (a) can be utilized in carrying outthe reaction of step (g). If desired, a molar excess of the halogenatingagent can be present, i.e., from about 2 to about 6 moles of thehalogenating agent per mole of the compound of formula V above. Thereaction or step (g) is carried out in the presence of an organic base.The organic base can be present in catalytic amounts. If desired, theorganic base can be added to the reaction medium in large amounts, i.e.,from about 1 mole to about 6 moles of the organic base per mole of thehalogen. In carrying out this reaction any conventional inert organicsolvent can be utilized. Among the conventional inert organic solventswhich can be utilized are included, dimethylformamide, benzene, toluene,etc. Generally, this reaction is carried out in an anhydrous medium.Furthermore, in carrying out this reaction, temperatures of from 50 C.to about 20 C. can be utilized. Generally it is preferred to carry outthis reaction at a temperature of from -35 C. to about 5 C.

The compound of formula IX above is converted, via step (h), to thecompound of formula I above by hydrogeuating the compound of formula IXwith a palladium catalyst in the presence of an alkali metal hydroxideat elevated pressures. Any conventional palladium catalyst such aspalladium, palladium on carbon, etc., can be utilized in carrying outthis hydrogenation reaction. In carrying out this reaction, anyconventional alkali metal hydroxide such as sodium hydroxide orpotassium hydroxide can be utilized. The palladium catalyst and thealkali metal hydroxide can be present in the reaction medium incatalytic quantities. However, if desired, large excess of the palladiumcatalyst or the alkali metal hydroxide can be utilized. Generally, thisreaction is carried out in a conventional inert organic solvent. Anyconventional inert organic solvent such as the solvents hereinbeforementioned can be utilized. The reaction of step (b) is carried out undera hydrogen pressure of from about 50 p.s.i.g. to about 1,000 p.s.i.g. Inthis reaction temperature is not critical and room temperature can beutilized. However, if desired, elevated temperatures can be utilized incarrying out this reaction. Generally, this reaction can be carried outat a temperature of from about 20 C. to about C.

In accordance with another embodiment of this invention, the compound ofthe formula V above is converted to the compound of the formula 1 viacompounds of the formulae X, XI and XII. In this embodiment, thecompound of the formula V above is first converted into the compound ofthe formula X above via reaction step (i) by saponification anddccarboxylation. The saponification step converts R into hydrogen in thecompound of the formula V above and this saponitied product is then decarboxylated to form the compound of formula X above. The reaction ofstep (i) is carried out utilizing the same conditions described inconnection with reaction step (f).

The compound of formula X above can be converted into the compound ofthe formula XI above via reaction step (j) by treating the compound ofthe formula X above with a halogenating agent in the manner described inconnection with step (a).

The preferred method of halogenation is to treat the compound of formulaX with an alkali metal hypohalite in an aqueous medium in the presenceof an alkali metal hydroxide.

In accordance with another embodiment of this invention, the compound ofthe formula XI above can be prepared from a compound of the formula VIIabove via reaction step (k). Reaction step (k) is carried out by firstsaponifying the compound of the formula VII so that R in the compound ofthe formula VII is hydrogen.

This saponified product is then decarboxylated to form a compound of theformula XI above. The saponification and decarboxylation in reactionstep ('k) is carried out utilizing the same conditions and in the samemanner described in connection with reaction step (f). Thedecarboxylation in step (k) is generally carried out at temperatures offrom to 30 C.

The compound of formula XI is converted to the compound of formula XIIby treating the compound of formula XI with a dehydrogenating agent asdescribed in connection with reaction step (d). The same conditionsutilized in connection with reaction step (d) are utilized in connectionwith reaction step (1). The preferred dehydrogenating agent for use incarrying out reaction step (1) is mercuric acetate in an organic acidsolvent such as acetic acid.

The compound of the formula XII above is converted into the compound ofthe formula I above via reaction step (m) by hydrogenating the compoundof the formula XII above with a palladium catalyst under elevated pressure. The same conditions described in connection with reaction step (h)are utilized in carrying out the reaction of step (In).

In connection with another embodiment of this invention, the compound ofthe formula X above can be converted into the compound of the formula Iabove by means of the following reaction scheme:

wherein R and R is lower alkyl or phenyl-lower alkyl and R is as above.

In accordance with this embodiment, the compound of formula X isconverted to the compound of the formula I above via compounds of theformula XIII and XIV. The compound of formula X above can be convertedto the compound of formula XIII above by any conventional means ofetherification. Among the methods of etherification which can beutilized to form the compound of formula XIII is to treat the compoundof formula X with a lower alkanol such as methanol, ethanol, etc., orphenyl-lower alkanol in the presence of a mineral acid such as hydrogenbromide, hydrogen chloride, etc. This reaction can be carried out, ifdesired, in an inert organic solvent medium. On the other hand, thelower alkanol or the phenyl-lower alkanol itself can be utilized as thesolvent medium. In this reaction, temperature and pressure are notcritical, and this reaction can be carried out at room temperature andatmospheric pressure or at elevated temperatures and pressures.

In accordance with this invention, either the compound of formula XIIIabove or the compound of formula X above can be converted to thecompound of formula XIV above by treating either the compound of formulaX or the compound of formula XIII above with cupric halide such ascupric chloride, cupric bromide, etc., in the presence of a loweralkanol or phenyl-lower alkanol. This reaction can be carried out, ifdesired, in a conventional inert organic solvent. On the other hand, thelower alkanol can be utilized as the solvent medium. In carrying out thereaction of either step (0) or step (r), temperature and pressure arenot critical, and these reactions can take place at room temperature andatmospheric pressure. On the other hand, elevated temperatures andpressures can be utilized if desired.

In accordance with a preferred embodiment of this invention the processof step (0) above can produce a new compound of the formula:

XIV-A wherein R is as above, R and R are independently selected fromphenyl-lower alkyl or lower alkyl with the proviso that the ether formedby R is a different ether from the ether formed by R The compound offormula XIV-A can be formed from the compound of formula XIII above byetherification via step (0). In forming the compound of the formulaXIV-A by step (0) a different alkanol or phenyl-lower alkanol isutilized than the alkanol or phenyl-lower alkanol utilized in forming Rin step (It). In this manner a diether of formula XIV-A is formedwherein the ether groups are not identical. Thus, the compound offormula XIV-A covers such compounds as:

3-ethoXy-S-methoxy-n-amylbenzene 3-isopropoxy-S-methoxy-n-pentylbenzene.

The compound of the formula XIV above is converted into the compound ofthe formula I above by any conventional method of ether hydrolysis.Among the conventional methods of ether hydrolysis that can be utilizedin carrying out reaction step (p), it is generally preferred to treatthe compound of the formula XIV with a mineral acid and salts of organicamine bases, such as those mentioned hereinbefore. Among the preferredare included, hydrobromic acid, and pyridine hydrochloride. Generally,this reaction is carried out in the presence of an inert organicsolvent. Any conventional inert organic solvent such as the solventsmentioned hereinbefore can be uti lized. In carrying out this reaction,temperature and pressure are not critical, and this reaction can becarried out at room temperature and atmospheric pressure. However, ifdesired, elevated temperatures and pressures can be utilized.

In accordance with another embodiment of this invention, the compound ofthe formula X above can be directly converted to the compound of theformula I above as in reaction step (q). This reaction is carried out bytreatin the compound of the formula X above with a dehydrogenatingagent. The same conditions described in connection with reaction step(d) can be utilized in carrying out the reaction of step (q). Among thepreferred dehydrogenating agents which can be utilized in carrying outreaction step (q), mercuric acetate is preferred. The preferred solventin this reaction is an organic acid solvent such as acetic acid.

The process of this invention can be utilized in preparing a variety ofresorcinols. By means of the process of this invention, the followingaldehydes can be converted to the following resorcinols via thefollowing Z-hydroxy- 4-oxo-cyclohex-2-enel-carboxylates of formula Vabove:

hexanal to 5-(n-pentyl)-resorcinol via methyl-6-n-pentyl-2-hydroxy-4-oxo-cyclohex-2-ene-l-carboxylate; butanal to5-(n-propyl)-resorcinol via methyl-6-n-propyl- 2-methyl-octanal to-(l-rnethylheptyl) resorcinol via Octanal to S-n-heptyl-resorcinol viamethyl-6n-heptyl-2- hydroxy-4-oxo-cyclohex-Z-ene- 1 -carboxylate;

Z-methyI-octanal to 5-(l-methylheptyl)-resorcin0l viamethyl-2-hydroxy-4-oxo-6-( 1-methylheptyl)-2-cyclohexene-l-carboxylate;

hendecanal to 5-(n-decyl)-resorcinol via methyl-Z-hydroxy-4-oxo-6-n'decyl -2-cyclohexene- 1-c arboxyl ate;

hexadecanal to S-(n-pentadecyl)-resorcinol via methyl-2-hydroxy-4-oxo-6-( l-pentadecyl)-2-cyclohexene-1- carboxylate;

docosanal to 5 -heneicosyl resorcinol via methyl-Z-hydroxy-4-oxo-6-(heneicosyl)-2-cyclohexene-l-carboxylate; and

hexacosanal to S-pentacosyl resorcinol via methyl-2- hydroxy-4-oxo-6-(pentacosyl) -2-cyclohexene-1- carboxylate.

tion provides a simple and economic means for synthe- U sizing valuableresorcinols.

The invention will be more fully understood from the specific exampleswhich follow. These examples are intended to illustrate the invention,and are not to be construed as limitative thereof. The temperatures ofthese examples are in degrees Centigrade, and the ether utilized inthese examples is diethyl ether.

EXAMPLE 1 Into a 2-liter three neck fiask fitted with a reflux condensertopped with a N gas inlet tube attached to a constant pressure mercurygauge, mechanical stirrer, dropping funnel and thermometer were placed230 ml. of anhydrous methanol (reagent grade) and 32.4 g. (0.60 mole) ofsodium methoxide. A slow current of N gas was introduced and the mixturewas stirred until a complete solution was obtained. One hundred and tengrams (0.68 mole) of diethyl malonate was added, the solution wasstirred for an additional minutes and 75 g. (0.48 mole) of 90% pure3-nonene-2-one was added portionwise at a rate such that the reactiontemperature was kept below the boiling point (ca. -60"). Stirring andrefluxing were continued for 3 hours. The reaction mixture was allowedto cool to room temperature, neutralized with concentrated HCl (-50 ml.)and allowed to stand overnight. The solvent was distilled under reducedpressure and the residue was partitioned between 200 ml. of 1 N HCl and800 ml. of ethyl acetate. The aqueous layer was separated and theorganic phase was washed with two 300 ml. portions of water and theproduct was then extracted from the ethyl acetate with a saturatedsolution of sodium bicarbonate until a small portion on acidification nolonger gave a turbid solution (:five 200 ml. portions). The sodiumbicarbonate solution was cautiously acidified and extracted with three300 ml. portions of ether. The ether solution was dried over sodiumsulfate and distilled under reduced pressure. The semi-solid residue wasdried at 50 under high vacuum for 5 hours to yield methyl6-n-pentyl-2-hydroXy-4-oxo cyclohex-Z- ene-l-carboxylate as a whitesolid, m.p. 8385.

EXAMPLE 2 Into a 2-liter three neck flask fitted with a refluxcondenser, mechanical stirrer, dropping funnel and thermometer wereplaced g. (0.25 mole) of methyl G-n-pentyl- 10 -2-hydroxy-4-oxo-cyclohex2-ene-1-carboxylate, 200 ml. of acetic acid and 200 ml. of water. Themixture was stirred vigorously until a fine suspension was obtained,cooled and maintained at 510 while 44.4 g. (0.28 mole) of bromine,dissolved in ml. of acetic acid, was added dropwise over a period of 2hours. The reaction was stirred at room temperature for 1 hour and thendiluted with 500 ml. of water and allowed to stand at 510 overnight. Thesolids were filtered, washed with cold water (ca. three ml. portions)until the washings gave a negative test for bromine and dried in avacuum oven at 50 for 4 hours to give methyl 3-bromo-2-hydroxy-4-oxo-6-n-pentyl-cyclohex-Z-ene-1-carboxylate, mp. 100- 102.

EXAMPLE 3 Into a 500 ml. three neck flask fitted with a refluxcondenser, mechanical stirrer and thermometer were placed 60 g. (0.182mole) of methyl 3-bromo-2-hydroxy-4-oxo-6-n-pentylcyclohex-2-ene-1-carboxylate and g. (0.75 mole) of anhydrouspyridine hydrochloride. The semisolid mixture was heated in an oil bathat 90 for 4 hours (internal temperature 8284) and then at 200 for 2hours. The reaction mixture was cooled to room temperature andpartitioned between 550 ml. of ether and ml. of 1.2 N HCl. The aqueouslayer was separated and the ether phase washed with 50 ml. of 1.2 N HCland then with 75 ml. of water. The organic phase was then washed withtwo 75 ml. portions of 10% sodium hydrosulfite (dithionite) followed bytwo 75 ml. portions of saturated NaHCO and then with 75 ml. of water,dried over anhydrous Na SO and the solvent evaporated under reducedpressure. The dark oil (34.6 g.) was distilled at 130/0.05 mm. Hg toyield olivetol.

EXAMPLE 4 30 g. (0.25 mole) of 92.4% pure 3-hepten-2-one and 52 g. (0.32mole) of diethyl malonate were reacted in the manner of Example 1 toproduce methyl 2-hydroxy- 4-oxo-6-n-propyl-2-cyclohexene-l-carboxylateas a white solid, m.p. 95-98".

EXAMPLE 5 3 g. (0.014 mole) of methyl2-hydroxy-4-oxo-6'n-propyl-2-cyclohexene-l-carboxylate was reacted inthe manner of Example 2 with 2.3 g. (0.014 mole) of bromine to produce,after crystallization from ethyl acetate, methyl 3 bromo 2hydroxy-4-oxo-6-n-propyl-2-cyclohexenel-carboxylate.

EXAMPLE 6 6 g. (0.021 mole) of methyl 3bromo-2-hydroxy-4-oxo-6-n-propyl-2-cyclohexene-l-carboxylate was reacted in the manner ofExample 3 with 9 g. (0.105 mole) of anhydrous pyridine HCl to give5-n.-propylresorcinol as a brown oil which was crystallized from waterand melted at 48-50.

EXAMPLE 7 192 g. (0.97 mole) of 85% pure 3-undecene-2-one was reacted inthe manner of Example 1 with 262 g. (1.65 moles) of diethyl malonate togive methyl-2-hydroxy 4-oxo-6-n-heptyl-2-cyclohexene-l-carboxylate as awhite solid, mp. 75-78.

EXAMPLE 8 268 g. (1 mole) of methyl Z-hydroxy-4-oxo-6-n-heptyl-2-cyclohexene-l-carboxylate was reacted in the manner of Example 2 with176 g. (1.1 moles) of bromine to give methyl 3 bromo 2hydroxy-4-oxo-6-n-heptyl-2-cyclohexene-l-carboxylate as a white solidmelting at 8487.

EXAMPLE 9 Into a 3-liter three neck flask fitted with a reflux condenserWith a Dean-Stark attachment, mechanical stirrer and thermometer wereplaced 348 g. (1 mole) of methyl 3-bromo-2-hydroxy 4 oxo6-n-heptyl-2-cyclohexenel-carboxylate and 522 g. (4.6 moles) ofanhydrous pyridine hydrochloride. The semi-solid mixture was heated inan oil bath at 90 for 4 hours (internal temperature 8284). The oil bathwas replaced with a mantle and the reaction mixture was heated(volatiles removed by means of the Dean-Stark take-off) until theinternal temperature reached 190-200 and maintained in this range for 2hours. The reaction mixture was cooled to room temperature andpartitioned between 3 liters of ether and 660 ml. of 1.2 N HCl. Theaqueous layer was separated and the ether phase washed with 300 ml. of1.2 N HCl and then with two 300 ml. portions of water. The ethersolution was extracted with four 350 ml. portions of a 10% NaOH solutionand the combined sodium hydroxide extracts were extracted with two 300ml. portions of ether. The alkaline aqueous solution was acidified withconcentrated hydrochloric acid (:700 ml.) and re-extracted with three800 ml. portions of ether. The combined ether extracts were washed withthree 300 ml. portions of 10% sodium hydrosulfite followed by two 300ml. portions of saturated NaHCOg and then with 300 ml. of water, driedover anhydrous Na SO and the solvent evaporated under reduced pressure.The dark oil (172.5 g.) was distilled. The forerun boiling at 140150/0.03 mm. Hg (8 g.) was discarded and the fraction boiling at 150155/0.02 mm. Hg was collected to give S-n-heptyresorcinol.

EXAMPLE 10 15 g. (0.078 mole) of 96.6% pure -methylundec-3- en-2-one wasreacted in the manner of Example 1 with 19 g. (0.12 mole) of diethylmalonate to give methyl-Z- hydroxy-4-oxo-6-(l-methylheptyl) 2cyclohexene 1- carboxylate as a white solid, mp. 8086.

EXAMPLE 11 20.2 g. (0.07 mole) of methyl-2-hydroxy-4-oxo-6-(l-methylheptyl)-2-cyclohexene 1 carboxylate was reacted in the mannerof Example 2 with 12 g. (0.072 mole) of bromine to produce 25.7 g. ofcrude methyl 3-bromo- 2-hydroxy-4-oxo-6-(1 methylheptyl) 2cyclohexenel-carboxylate. The crude methyl 3-bromo-2-hydroxy-4-oxo-6-(1-methylheptyl) 2 cyclohexene-l-carboxylate was treated with 32g. (0.27 mole) of anhydrous pyridine hydrochloride by the procedure setforth in Example 3 to give 5-(l-methylheptyl)resorcinol as a colorlessoil boiling at 129/0.04 mm. Hg.

EXAMPLE 12 A mixture of 5 g. (0.021 mole) of methyl 6-n-pentyl-2-hydroxy-4-oxo-cyclohex-2-enel-carboxylate, 5.5 g. (0.021 mole) of iodineand 50 ml. of acetic acid was stirred at room temperature for 24 hours.The solvent was evaporated under reduced pressure and the residuepartitioned between Water and ethyl acetate. The aqueous phase wasseparated and the ethyl acetate solution extracted with two 100 ml.portions of sodium bicarbonate. The bicarbonate solution was acidifiedand extracted with two 100 ml. portions of ethyl acetate. The ethylacetate extracts were combined, washed with water, dried over anhydroussodium sulfate and evaporated under reduced pressure to give methyl3-iodo-2-hydroXy-4-oxo-6-n-pentyl-2-cyclohexene-l-carboxylate, mp.109-112".

EXAMPLE 13 A mixture of 2.4 g. (0.01 mole) of methyl 6-n-pentyl-2-hydroxy-4-oxo-cyclol1ex-Z-ene-l-carboxylate and 3.4 g. (0.015 mole) ofdichlorodicyanoquinone in 100 ml. of benzene was stirred and refluxedfor 8 hours. The reaction mixture was allowed to cool to roomtemperature and the precipitate filtered. The filtrate was washed withwater, then with two 75 ml. portions of a Na CO solution and thenextracted with two 75 ml. portions of a 5% NaOH solution. The sodiumhydroxide solution was acidified with 6 N hydrochloric acid andextracted with two 150 ml. portions of ethyl acetate. The organic phasewas washed with water, dried over anhydrous sodium sulfate and distilledunder reduced pressure to give methyl 2,4-dihydroxy-G-n-pentylbenzoateas a viscous oil.

EXAMPLE 14 A mixture of 2.4 g. (0.01 mole) of methyl 6-n-pentyl-2-hydroxy-4-oxo-cyclohex-2-ene-l-carboxylate and 1.5 g. of 25% Pd/C washeated at 230240 for 3 hours. The reaction mixture was allowed to coolto room temperature, 100 ml. of benzene was added and the resultingsuspension warmed on a steam bath and filtered hot. The filtrate wasdried over anhydrous sodium sulfate and evaporated under reducedpressure to give 0.9 g. (38%) of methyl 2,4-dihydroxy-6-n-pentylbenzoateas a viscous oil.

EXAMPLE 15 A mixture of 2.4 g. (0.01 mole) of methyl 6-n-pentyl-2-hydroxy-4-oxo-cyclohex-2-ene-l-carboxylate and 3.4 g. (0.011 mole) ofmercuric acetate in 50 m1. of acetic acid was stirred and refluxed for 4hours, cooled to room temperature and the solution decanted from themetallic mercury. The solvent was distilled under reduced pressure andthe residue partitioned between 100 ml. of ethyl acetate and 50 ml. ofwater. The organic phase was extracted with two 100 ml. portions ofsodium bicarbonate, two 50 ml. portions of 1% NaOH solution and thenwith 50 ml. of water, dried over anhydrous sodium sulfate and evaporatedunder reduced pressure. The oily residue (1.3 g.) was crystallized fromether to give methyl 2,4-dihydroxy-6-npentylbenzoate, mp. 73-75".

EXAMPLE 16 A mixture of 6.4 g. of (0.02 mole) of methyl 3-iodo-2-hydroxy-4-oxo-6-n-pentyl-cyclohex-2-ene-1 carboxylate and 2 g. (0.022mole) of pyridine in 50 ml. of 1,2,4-trichlorobenzene was stirred at95l00 (internal temperature) for 2 hours. The mixture was cooled, washedwith two ml. portions of 1.2 N HCl, then with two ml. portions of water,followed by two ml. portions of a 1:1 parts by volume mixture ofsaturated solution of sodium bicarbonate and sodium carbonate and thenextracted with three 100 ml. portions of 5% by weight NaOH solution. Thealkaline solution was acidified with 6 N HCl and extracted with three100 ml. portions of ethyl acetate. The combined ethyl acetate extractswere washed with water, dried over anhydrous Na SO and the solventremoved under reduced pressure to give methyl 2,4-dihydroxy-6-n-pentylbenzoate as a viscous oil.

EXAMPLE 17 A mixture of 4.8 g. (0.02 mole) of methyl 6-n-pentyl-2-hydroxy-4-oxo-cyclohex-2-ene-l-carboxylate and 100 ml. of acetic acidwas stirred vigorously at 75 until a fine suspension was obtained. Themixture wass cooled and maintained at 510 while a solution of 3.9 g.(0.021 mole) of bromine dissolved in 10 ml. of acetic acid was addeddropwise over a period of 1 hour. The reaction mixture was allowed tostir at room temperature for 1 hour and then on a steam bath for 3hours. The solvent was evaporated under reduced pressure and the oilyresidue dissolved in 200 ml. of ether, washed with two 25 ml. portionsof 10% sodium hydrosulfite, followed by two 25 ml. portions of saturatedNaHCO and then with water, dried over anhydrous Na SO and evaporatedunder reduced pressure to give olivetol.

EXAMPLE 18 A mixture of 4.8 g. 0.02 mole) of methyl 6-n-pentyl-2-hydroxy-4-oxo-cyclohex-2-ene-l-carboxylate and 5.6 g. 0.021 mole) ofiodine in 200' ml. of acetic acid was stirred and heated to reflux for10 hours. The solvent was removed under reduced pressure and the oilyresidue was dissolved in 250 ml. of ether and washed with two ml.portions of water. The ether layer was then washed with two 25 ml.portions of an aqueous solution containing 20% by weight sodiumhydrosulfite, followed by two 25 ml. portions EXAMPLE 19 A mixture of12.2 g. (0.05 mole) of methyl 6-n-pentyl-2-hydroxy-4-oxo-cyclohex-Z-ene-l-carboxylate and 100 ml. of acetic acidwas stirred vigorously at 25 until a fine suspension was obtained. Itwas cooled and maintained at 10 while 22.4 g. (0.1 mole) of cupricbromide dissolved in 25 ml. of acetic acid was added dropwise over aperiod of 1 hour. The reaction mixture was allowed to stir at roomtemperature for 1 hour and then at steam bath temperature for 3 hours.The solvent was evaporated under reduced pressure and the residuepartitioned between 200 ml. of water and 300 ml. of ether. The etherextracts were washed with two 50 ml. portions of an aqueous solutioncontaining by weight sodium hydrosulfite, followed by two 35 ml.portions of saturated NaHCO and then with 75 ml. of water, dried overanhydrous Na SO and the solvent evaporated under reduced pressure togive olivetol.

EXAMPLE A mixture of 52 g. (0.16 mole) of methyl 3-bromo-2-hydroxy-4-oxo-6-n-pentyl-cyclohex 2 ene 1 carboxylate and 200 ml. ofconcentrated hydrochloric acid in 100 ml. of acetic acid was stirred andrefluxed for 14 hours. The solvent was removed under reduced pressureand the residue was dissolved in 500 ml. of ether. The organic phase waswashed with 200 ml. of water, then with two 50 ml. portions of anaqueous solution containing 10% by weight of sodium hydrosulfite,followed by two 75 ml. portions of saturated NaHCO and then with 75 ml.of water and dried over anhydrous Na SO The solvent was evaporated underreduced pressure to give a dark oil (28.8 g.) which was distilled atl135/0.2 mm. Hg to yield olivetol.

EXAMPLE 21 A mixture of 52 g. (0.16 mole) of methyl 3-bromo-2 hydroxy 4oxo-6-n-pentyl-cyclohex-2-ene-l-carboxylate and 200 ml. of an aqueoussolution containing 48% by weight of hydrobromic acid in 100 ml. ofacetic acid was stirred and refluxed for 3 hours. The solvent wasremoved under reduced pressure and the residue was dissolved in 500 ml.of ether. The ether phase was washed with two 100 ml. portions of waterand then with two ml. por tions of 10% sodium hydrosulfite, followed bytwo 75 ml. portions of saturated NaHCO and then with 75 ml. of water,dried over anhydrous Na SO and the solvent evaporated under reducedpressure. The dark oil (30.1 g.) distilled at 130140/0.2 mm. Hg to yieldolivetol.

EXAMPLE 22 A mixture of 24 g. 0.1 mole) of methyl 2,4-dihydroxy-6-n-pentylbenzoate and 200 ml. of a 10% by weight NaOH solution washeated on a steam bath for 7 hours. The solution was cooled, extractedwith two 100 ml. portions of ether, and slowly acidified withconcentrated hydrochloric acid. The aqueous phase was heated at steamtem perature for 1 hour longer, cooled and extracted with three 200 ml.portions of ether. The extracts were combined, washed with two 75 ml.portions of water, then with two 50 ml. portions of an aqueous solutioncontaining 10% by weight of sodium hydrosulfite, followed by two 50 ml.portions of water, dried over anhydrous Na SO and the solvent wasremoved under reduced pres sure to give olivetol.

EXAMPLE 23 A solution of 50 g. (0.208 mole) of methyl 6-n-pentyl-Z-hydroxy-4-oxo-cyclohex-2-ene 1 carboxylate in 200 ml. of an aqueoussolution containing 20% by weight of NaOH was heated on a steam bath for2.5 hours, cooled and extracted with two 100 ml. portions of ether. The

14 alkaline aqueous solution was acidified slowly with about ml. ofconcentrated hydrochloric acid. The resulting aqueous mixture wasstirred and heated on a steam bath for 1 hour longer, cooled andextracted with three 200 ml. portions of ether. The ether extracts werewashed with water, dried over anhydrous sodium sulfate and the solventwas evaporated under reduced pressure. The residue was treated twicewith 50 ml. of benzene, distilling the solvent each time, to leaveI3-hydroxy-5-n-pentyl-2- cyclohexene-l-one as a viscous oil whichsolidified on standing.

EXAMPLE 24 A solution of 30 g. (0.094 mole) of methyl 3-bromo-2-hydroxy-4-oxoG-n-pentyl-cyclohex 2 ene 1 carboxylate in 200 ml. of anaqueous solution containing 10% by weight of NaOH was heated on a steambath for 2 hours. The mixture was cooled to 0-5 which was maintainedwhile 6 N HCl Was added slowly with stirring until an acidic solutionwas obtained. The reaction mixture was allowed to warm to roomtemperature and stirred overnight. The resulting semi-solid mixture wasdissolved in 500 ml. of ethyl acetate, washed with three 50 ml. portionsof water and extracted with three 150 ml. portions of saturated aqueousNaHCO The stirred bicarbonate solution was acidified with dilute HCl andthe mixture allowed to stand overnight. The precipitate was filtered,washed with water and dried in a vacuum oven at 50 for 4 hours to give2-bromo-3-hydroxy-5-n-pentyl- 2-cyclohexene-1-one, mp. 135-138.

EXAMPLE 25 To a stirred solution of 18.2 g. (0.1 mole) of 3-hydroxy-S-n-pentyl-Z-cyclohexene-l-one in 300 ml. of a 5% NaOH solution whichwas maintained at. 5-10, 45.6 ml. of a 17% by weight (0.11 mole) aqueoussodium hypochlorite solution was added over 1 hour. The mixture wasstirred at room temperature for 2 hours and then at 50 for 30 minutes,cooled to 4, acidified with 6 N HCl and allowed to stir overnight. Theprecipitate that formed was filtered, washed with water and dried togive 2-chloro-3-hydroxy- 5-n-pentyl-2-cyclohexen-l-one, m.p. 125-129,

EXAMPLE 2.6

A mixture of 4.3 g. (0.02 mole) of 2-chloro-3-hydroxy-5-n-pentyl-2-cyclohexen-1-one, 6.4 g. (0.02 mole) of mercuric acetate inml. of acetic acid was stirred and refluxed for 4 hours. The solutionwas decanted from the metallic mercury and the solvent was removed underreduced pressure. The oily residue was dissolved in 200 ml. of anaqueous solution containing 10% by weight NaOH, 10 g. of sodiumhydrosulfite was added and the mixture was heated at 50 for 20 minuteswith occasional shaking. The mixture was allowed to cool to roomtemperature and filtered by gravity. The filtrate was extracted with two50 ml. portions of ether and acidified with 6 N HCl and ex tracted withthree 75 ml. portions of ether. The combined ether extracts were washedwith three 50 ml. portions of sodium bicarbonate, dried over anhydrousNa SO and the solvent was removed under reduced pressure. The oilyresidue was purified by dry column chromatography, using silica gel asthe absorbent and a mixture of 97 parts by volume benzene: 3 parts byvolume ethyl acetate as the developing agent, to give2-chloro-5-n-pentylresorcinol: b.p. 300/760 mm. Hg.

EXAMPLE 27 A stirred mixture of 24 g. (0.1 mole) of methyl6-npentyl-2-hydroxy-4-oxo-cyclohex 2 ene 1 carboxylate, 50 ml. ofpyridine and 50 ml. of dimethylformamide was stirred and cooled at 30and maintained at this temperature while 48 g. (0.3 mole) of bromine wasadded dropwise over a period of 2 hours. The reaction mixture wasallowed to warm to room temperature, stirred at this temperatureovernight and the volatiles were evaporated under reduced pressure. Theresidue was dissolved in 300 ml. of ethyl acetate, washed with three 100ml. portions of water and then with three 250 ml. portions of asaturated NaHCO The organic phase was extracted with three 150 ml.portions of an aqueous solution containing 5% by weight of NaOH, thealkaline aqueous solution acidified with 6 N HCl and extracted with two400 ml. portions of ethyl acetate. The organic extracts was dried overNa SO and the solvent was removed under reduced pressure to give3,5-dibromo 2,4 dihydroxy-6-n-pentylbenzoic acid methyl ester as a darkoil.

EXAMPLE 28 A solution of 91 g. (0.5 mole) of 3-hydroxy-5-n-pentyl-2-cyclohexene-l-one in 300 ml. of 5% by Weight of hydrogen bromidein methanol was stirred at room temperature for 24 hours. The volatileswere removed under reduced pressure and the oily residue was dissolvedin 700 ml. of ether, extracted with four 150 ml. portions of a saturatedaqueous Na CO solution, washed with 150 ml. of water, dried overanhydrous Na SO and then distilled at 109/ 0.06 mm. Hg to give3-methoxy-5-n-pentyl-2-cyclohexenel-one.

EXAMPLE 29 A mixture of 18 g. (0.1 mole) of 3-hydroxy-5-n-pentyl-2-cyclohexene-1-one and 34.1 g. (0.2 mole) of cupric bromide in 300 ml.of methanol was stirred at room temperature for 24 hours, filtered andthe filtrate evaporated under reduced pressure. The residual oil waspartitioned between 300 ml. of ether and 150 ml. of water. The etherlayer was separated, washed with two 150 ml. portions of saturated Na COsolution, 100 ml. of water and dried over anhydrous Na SO andevaporated. The dark oil was fractionally distilled to give3,4-dimethoxy-n-amylbenzene, b.p. l/0.05 mm. Hg.

EXAMPLE 30 A mixture of 3.6 g. (0.02 mole) of3-methoxy-5-n-pentyl-2-cyclohexene-1-one and 6.8 g. (0.04 mole) ofcupric bromide in 100 ml. of methanol was reacted by the procedure givenin Example 29 to afford 3,5-dimethoxy-namylbenzene.

EXAMPLE 31 To a solution of 36 g. (0.2 mole) of3-hydroxy-5-npentyl-2-cyclohexene-l-one in 500 ml. of acetic acid, 77 g.(0.241 mole) of mercuric acetate was added and the mixture was stirredand refluxed for 7 hours. After standing overnight, the solution wasdecanted from the metallic mercury that had formed and the solvent wasevaporated under reduced pressure. The dark brown oily residue wasdissolved in 400 ml. of an aqueous solution containing 10% by weight ofNaOH, g. of sodium hydrosulfite was added and the mixture was heated ona steam bath for 30 minutes. Charcoal (3 g.) was then added, the mixturewas heated for an additional 10 minutes, filtered by gravity and thecake was washed with an aqueous solution containing 10% by weight NaOHsolution. The combined filtrates were neutralized to pH 6.5-7 withconcentrated hydrochloric acid and extracted with three 250 ml. portionsof ether. The ether extracts were washed with two 70 ml. portions of asaturated solution of sodium sulfite, two 75 ml. portions of a 1 part byvolume to 1 part by volume mixture of saturated solutions of Na CO andNaI-ICO water, dried over anhydrous Na SO and then the solvent wasevaporated under reduced pressure. The dark oil (31 g.) was distilledusing a small fractionating column. The first fraction (2.4 g.) boilingat 105-120/ 0.1 mm. Hg was discarded and the fraction boiling at l20130/0.04 mm. Hg was collected to afford olivetol.

EXAMPLE 32 A mixture of 2.14 g. (0.01 mole) of 2-chloro-5-n-penyl-resocinol and 5.6 g. (0.04 mole) of KOH in 50 ml.

16 of methanol was heated in an autoclave with 2 g. of Pd/C at 50 and100 p.s.i.g. for 5 hours. The catalyst was filtered, washed with three20 ml. portions of ethanol and the filtrate was evaporated under reducedpressure to give olivetol.

EXAMPL'E 33 A mixture of 3.9 (0.01 mole) of 3,5-dibromo-2,4-dihydroxy-6-n-pentylbenzoic acid methyl ester and 5.6 g. (0.04 mole) ofKOH in 50 ml. of ethanol was hydrogenated in an autoclave with 2 g. ofPd/ C at 50 and 100 p.s.i.g. for 5 hours. The catalyst was filtered,washed with three 20 ml. portions of ethanol and the combined filtratewas evaporated under reduced pressure to give olivetol.

EXAMPLE 34 Into a 2-liter three neck creased flask equipped withthermometer, stirrer, condenser and Hershberg dropping funnel was placed100 ml. of 2.5 N sodium hydroxide and 348 g. (6 moles) of acetone. Themixture (under a nitrogen atmosphere) was heated to 54 with an oil bathand, while stirring rapidly, a solution of 200 g. of 2-methyl-1- octanalin 232 g. (4 moles) of acetone was added dropwise over a period of 3hours. After completion of the addition, stirring was continued for anadditional 30 minutes at 54, the reaction mixture was cooled to 10, and83 ml. of 3 N hydrochloric acid was added to pH 4.5. Anhydrous magnesiumsulfate (240 g.) was added with cooling, stirred 30 minutes and themixture filtered. 'Ihe filtrate was concentrated at reduced pressure togive a residual brown oil weighing 369.2 g., which was dissolved in 1liter of benzene and further dried over anhydrous magnesium sulfate.After removal of the drying agent by filtration, 136.8 g. (0.856 mole)of anhydrous powdered cupric sulfate was added and the mixture wasstirred and refluxed for 18 hours. During this reflux period about 20ml. of water was azeotropically removed with a Dean- Stark assembly. Oncooling to room temperature, the copper sulfate was removed byfiltration and the presscake was washed with three 200 ml. portions ofbenzene. The combined benzene filtrates were concentrated at reducedpressure to give 322.5 g. of a residual brown oil which was distilledthrough a 9-inch Vigreux column. After separation, the product 5-methylundec-3-en-2-one was collected in two fractions: 125.7 g., b.p.77-80/6.5 mm. Hg aiifi 25.2 g., b.p. 8083.

EXAMPLE 35 A mixture of 100 g. of 3,S-dimethoxy-n-amylbenzene and 600 g.of pyridine hydrochloride in a 2-liter 3-neck flask equipped withmechanical stirrer is heated with a mantle and allowed to distill untilthe temperature of the vapors reach 210 (usually 5-10 ml. ofdistillate). A reflux condenser is then added and the solution isheated,

under reflux for minutes. The reaction is allowed to cool to below and 1liter of 2 N hydrochloric acid is added. The cooled solution is thenextracted four times each time with 1 liter of ethyl acetate. Theextracts were dried (Na SO concentrated under vacuum and then distilledunder high vacuum to give olivetol, boiling point (1 mm. Hg).

EXAMPLE 36 A mixture of 3.6 g. (0.02 mole) of3-methoxy-5-n-pentyl-2-cyclohexen-1-one and 6.8 g. 60.04 moles of cupricbromide in 100 ml. of benzyl alcohol was reacted by the procedure ofExample 29 to produce 3-benzyloxy-5-meth oxy-n-amylbenzene.

EXAMPLE 37 100 g. of 3-benzyloxy-S-methoxy-n-amylbenzene was reacted inthe manner of Example 35 to produce olivetol.

3,850,997 17 18 What is claimed is: OTHER REFERENCES 1. The compound2-ch1oro-S-n-pentylresorcinol.

References Cited BERNARD HELFIN, Primary Examiner UNITED STATES PATENTS5 W. B. LONE, Assistant Examiner 2,093,773 9/1937 Kyrides 260154Chuzaburo Mahnami: Chem. Abs., vol. 47, p. 287%.

1. THE COMPOUND 2-CHLORO-5-N-PENTYLRESORCINOL.